http://circres.ahajournals.org/content/113/5/492.extract.html?etoc
Although detrimental
effects of tumor necrosis factor-α (TNF-α) have been reported in
failing myocardium, clinical trials
using TNF-α antagonists did not show the
benefit of TNF-α inhibition in patients with chronic heart failure
(CHF). The double-edged
effects of TNF-α/Toll-like receptors
(TLRs)–related proinflammatory cytokines and downstream signal
transduction, nuclear
factor (NF)-κB activation on failing
myocardium are discussed.
It is well known that neurohormonal
activation in heart failure plays a key role in deterioration of
myocardial failure, accelerating
the vicious cycle in pathophysiology of heart
failure. Proinflammatory cytokines are also increased in patients with
heart
failure. Since the first report by Levine et
al1 that serum TNF-α is
increased in patients with severe heart failure, other cytokines, such
as interleukin-1β (IL-1β), interleukin-6
(IL-6), and their soluble receptors, have
been reported to increase in heart failure.2 Several reports indicated that plasma levels of these proinflammatory cytokines are correlated with severity of heart failure,
New York Heart Association functional class.3 The question was whether these proinflammatory cytokines deteriorate the failing myocardium as a cause of detrimental mechanism
or merely secondary phenomenon in heart failure.
To answer this question, Kubota et al4
established a murine transgenic line of TNF-α in which expression was
driven by the murine α-myosin heavy chain promoter.
The transgenic heart with chronic
overexpression of TNF-α showed (1) ventricular hypertrophy, (2)
ventricular dilatation,
(3) interstitial infiltrates, (4)
interstitial fibrosis, (5) rare myocyte apoptosis, (6) a diminished
ejection fraction, (7)
attenuation of β1-adrenergic responsiveness,
and (8) expression of atrial …
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